SK277758B6 - Transdermal therapeutic system - Google Patents

Abstract

Transdermal therapeutic system has the storage of effective substance, which creates multi-chamber system, in which are settled the separating chambers (14). These separating chambers (14) are separated and contain at least one effective substance, at which between reverse layer (10) and fixed device is at least one self-adhesive layer (19).

Description

Technical field

The invention relates to a transdermal therapeutic system for the administration of active ingredients to the skin, with a backsheet facing away from the skin, an active substance depot, an active substance dosing control device that controls the active substance dosing system and a fixation device adhering the therapeutic system to the skin this system.

BACKGROUND OF THE INVENTION

Types of transdermal active substance reservoir system have been known, for example, from DE 36 29 304 according to which one or more isolated active substance reservoirs are arranged without any interconnection in the active substance distribution matrix.

This known arrangement is particularly suitable for solid or highly viscous materials, whereby the highly concentrated active substance is deposited in the active substance distribution matrix to be released from there through a control membrane - adhered by pressure.

With regard to active liquid substances or active substance preparations, the active substance is often deposited in a bag-like recess of the matrix or in a bag formed of a control membrane or foil, whereby when the active substance reservoir is emptied, the internal pressure rapidly decreases and thus the active substance migration rate. A further drawback of large pocket systems with a fluid active ingredient preparation is that they are pressure sensitive; when the system is under pressure, all the active substance exits uncontrollably from the ruptured pouch into the active substance distribution matrix and the dosing to the skin is not controlled. This is particularly undesirable when it is a highly active substance with an overdose leading to risk.

A further drawback of the known systems is that they are indivisible and, for example, for children and adults, or for patients in need of lower doses of active ingredient, different sizes of transdermal therapeutic systems must be made available.

Finally, in the patch with a large fluid reservoir, due to the gravity force effect, the fluid distribution is irregular, which greatly affects the uniformity of dosage of the active ingredient.

Accordingly, it is an object of the present invention to overcome the aforementioned drawbacks of the prior art and to provide a new transdermal system which allows for a safer handling especially with respect to liquid active substances or preparations thereof.

SUMMARY OF THE INVENTION

This object is achieved according to the invention by a transdermal therapeutic system, the reservoir of the active substance being a multi-chamber system, in which the chambers which are separated contain at least one active substance, wherein there is at least one self-adhesive layer between the backing layer and the fixation device.

The multi-chamber system is advantageous because the distribution of the active ingredient is better, and optionally, if a portion of the transdermal therapeutic system area is severed (cut off), there is no need to worry that all of the formulation will leak or fall out. Furthermore, the active substance-containing liquid preparations can be displaced only to a limited extent by the action of gravity or pressure, so that a fairly uniform distribution of the active-substance-containing liquid can be achieved even under the action of a gravity force. If one chamber containing the active substance bursts due to the pressure load, the other chambers will remain undamaged, so that the system function will still be preserved anyway - a safety measure that will reduce the risk of overdosing with high-performance liquid substances.

A further advantageous embodiment of the invention consists in that the individual chambers are connected at least partially by channels and hence between each other, so that it is possible for the contents of one chamber to flow out to equalize the pressure.

It may also be advantageous if the connecting channels between the chambers have an inside diameter which allows the flow of active substance fluid only under pressure. This embodiment avoids the rupture of the container and thus the inapplicability of the system under pressure loading, for example when used on animals for veterinary medical purposes, such a pressure distribution device is useful.

It is also possible for the multi-chamber system to be designed as a channel system.

The chambers can optionally be equipped with different active substance dispensing devices. This embodiment makes sense if different active substances are to be used in one system and the active substance is to be dosed on the skin at different dosing rates.

The chambers may be arranged in one or more identical or different matrices for distributing the active substances, which may be arranged one above the other and / or side by side.

The transdermal therapeutic system of the invention preferably has a continuous or intermittent self-adhesive layer as a skin fixation device.

The transdermal therapeutic system may further comprise one or more self-adhesive layers between the backing layer and the fixation device. This is necessary and makes sense in particular when the active substance distribution matrix is not self-adhesive and the impermeable backing layer can be applied with only one additional self-adhesive layer.

The system according to the invention is particularly advantageous when used with a liquid substance or liquid active substances, or when these are in solution.

In a multi-chamber system, there may be a desired break line between the individual chambers and optionally in the backing layer with other layers. Such breakpoint lines allow the system to be divided if it is desired to release a smaller dose of the active ingredient. This can, for example, prevent costly storage of transdermal therapeutic systems of varying sizes and doses.

The chambers can be arranged at different height levels of the patches, or in distribution matrices.

The multi-chamber system can be arranged in a self-adhesive matrix separating the active substance and a control matrix.

The multi-chamber system may in this case be composed of films filled with a solution of active substances or of an active substance which have a controlling effect and which may be permeable to the active substance or possibly controllable permeable and may be welded together to form a multi-chamber system.

The therapeutic system according to the invention can be used for the packaging and administration of transcutaneously usable active substances for human and veterinary medicine as well as for cosmetics.

The container may also contain inert substances. By inert is meant here that the active ingredient and the excipient do not react together; the inert excipient may also be a substance exhibiting physiological effects, such as DMSO and the like, which, for example, increases skin permeability. Protective materials are also offered as such adjuvants which impart pressure and tensile resistance to the active substance reservoir as well as carriers.

The active substances which can be used are transdermally usable active substances. Typical examples of these are: nicotine corticosteroids: hydrocortisone, prednisolone, beclomethasone propionate, flumethasone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinoline acetonide, clobetazolpropinate, etc., analgesic agents, diclofenaclofenone, diclofenaclofenone, antiinfeflamiclofenone. phenylbutazone, flurbiprofen, salicylic acid, 1-menthol, camphor, sulindac-tolmetin-sodium, naproxen, fenbufen, etc., hypnotic effective sedatives: phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepam, lorazepam, haloperidinizine, tranquidazin, tioroperidine, etc., , lorazepam, flunitrazepam, chlorpromazine, etc., antihypertensive drugs: pindolol, bufralol, indenolol, nifedipine, nipradinol, bucumolol etc., antihypertensive diuretics: hydrothiazide, bendroflumethiazide, floblobiciline, tetrobenzothiazine, cyclobenzothiazine, cyclobenzothiazine, cyclobenzothiazine, cycllobenziline, penlobenziline , erythromycin, chloramphenicol, etc., anesthetics: lidocaine, benzocaine, ethylaminobenzoate, etc., antimicrobial agents: benzalkonium chloride, nitrafurazone, nystatin, acetosulfamine, clotrimazole, etc., antifungicidal agents: pentamycin, clototerin, clototerin, clototericin, amphotericin; vitamin A, ergocalciferol, cholecalciferol, octothiamine, riboflavin butyrate etc., antiepileptics: nitrazepam, meprobamate, clonazepam etc., coronary vasodilators: nitroglycerol, dipyridamol, erythritetranhydrate, pentaerythritatenyl, pentaerythritatenyl. antitussives: dertromethosphane (hydrobromide), terbutaline (sulphate), ephedrine (hydrochloride), salbutanol (sulphate), isoproteranol (sulphate, hydrochloride), etc., sex hormones: progesterone etc., thymoleptics: dexepine, etc., other drugs: 5-fluoruracil , fentanyl, desmopressin, demperdone, scopolamine (hydrobromide), peptide, etc., of course, this list is not exhaustive.

Advantageously, the active substance matrix may be layered, the layers being the same or different. The active substance matrix may be self-adhesive, for example it may be a rubber material such as styrene / isoprene / styrene block copolymers, silicone rubber or even synthetic resins such as poly / meth / acrylate, polyurethane, polyvinyl ether, polyester or the like; a summary of suitable materials for the matrix can be found, for example, in DE-OS 35 00 508, the content of which has been taken into account. It may be advantageous if the container matrix is self-adhesive, since it is then possible to dispense with a separate self-adhesive device in the system; the use of such a self-adhesive matrix depends on, inter alia, the compatibility of the matrix material with the active ingredient. Self-adhesive materials for matrices are known.

Preferred non-adhesive matrix materials are: polymers composed of poly / meth / acrylate, polyvinylpyrrolidone, ethylcellulose, hydroxypropylcellulose, hydroxymethylcellulose phthalate, polyvinyl alcohol, or copolymers thereof with vinyl laurate or maleic acid, vinyl acetate or copolymer thereof, maleic acid; polyvinyl ether, butyl rubber and polycaprolactan.

For example, the chambers may also be arranged between the backsheet of the reservoir matrix and the reservoir matrix layer facing the skin.

The backing layer used may be materials known per se, impermeable to the active substance, such as metal foils, plastic foils or laminates thereof, which are known to the person skilled in the art.

BRIEF DESCRIPTION OF THE DRAWINGS

Further advantages and features will become apparent from the following description, in which: FIG. FIG. 1 shows a therapeutic system according to the invention in cross-section; Fig. 2 shows another system according to the invention in cross-section; Fig. 3 shows another system according to the invention in cross-section; Fig. 4 shows a system according to the invention with channels in top view of a system having a backsheet removed; Fig. 5 shows a further embodiment of the invention with respect to the backsheet system; Fig. 6 shows another embodiment of the invention in cross-section; Fig. 7 shows a further embodiment of the invention when the backing layer with the channel system is removed; Fig. 8 shows an embodiment of a system according to the invention with a non-straight channel system in cross-section; Fig. 9 is a cross-sectional view of another transdermal system of the invention, and; Fig. 10 shows an embodiment of the system according to the invention in perspective when removing the backing layer with the desired break lines.

DETAILED DESCRIPTION OF THE INVENTION

In FIG. 1 shows a first preferred embodiment of the system according to the invention in the form of a patch transdermal system in cross-section. The system has a backing layer 10 which is impermeable to the active substance, for example a metal foil or a polymer foil. The backing layer 10 may also be formed from a laminate of various materials. Under the backing layer 10 is an active substance distribution matrix 12 which is made of a material permeable to the active substance. Self-crosslinking acrylate copolymers are suitable, for example, for such an active substance distribution matrix 12, which is preferably self-adhesive in this embodiment. however, the distribution matrix 12 is also dependent on the active ingredient used. They are filled with a liquid active substance, such as a nicotine solution, in the distribution matrix 12. Between the individual chambers 14, the two active agent layers adhere to each other to prevent nicotine from flowing freely into the entire chamber system 14. The active agent, here nicotine, dissolves in the distribution matrix 12, the release rate from the transdermal system being determined inter alia by the diffusion rate In the active substance distribution matrix 12 which completely surrounds the active substance distribution chambers 14, a self-adhesive layer 19 is applied which is suitable for attaching the system to the skin. Furthermore, the pressure-sensitive adhesive layer 19 is permeable to the active substance and may optionally have a controlling effect of the dosage of the active substance.

In FIG. 2 is a further preferred embodiment of the patch therapeutic system according to the invention in cross-section, in which distribution chambers 14, 14 'are formed in two different active substance distribution matrices 12, 12', which may contain, for example, different active substances or preparations containing active substances. substances. Both active ingredient distribution matrices 12, 12 'can be selected with respect to the requirements of the desired active substance dosing rate. The system has a continuous adhesive layer 19 for adhering to the skin, for attaching the system to the skin, wherein the adhesive may also have some control effect.

In FIG. 3 shows a manufacturing-simple embodiment of the invention, in which the distribution chambers 14 are formed in a self-adhesive active substance distribution matrix 12 whose adhesion properties are also sufficient to attach the system to the skin.

In FIG. 4 is a further preferred embodiment of the transdermal therapeutic system according to the invention, in which the active substance distribution chambers 14 are interconnected by channels 15 so that, for example, when locally applying pressure to the system, the active substance-containing liquid contained in the channel system 15 can flow. to equalize the pressure.

In FIG. 5 shows a system according to the invention in which the multi-chamber system is composed of grid-like active substance channels 15. Here again, the backsheet 10 is removed to allow observation of the drug reservoir.

Fig. 6 shows an embodiment of the invention in which the individual regions of the pressure-sensitive adhesive layer 19 are arranged in the active substance distribution matrix 12 for fixing the system to the skin, while the active substance dosing is carried out mainly through non-adhesive or low adhesive areas of the active substance distribution matrix.

In FIG. 7 shows an embodiment where the distribution chambers 14 are configured as concentric annular channels 15, and different active substances can also be stored in the individual concentric annular channels 15.

In FIG. 8 is another embodiment of a system similar to that of FIG. 3 in that there is also used a self-adhesive active substance distribution matrix 12 in which there is a channel system 15 which contains the active substance or a liquid containing the active substance. The channel system is arranged with variable heights. This arrangement is advantageous, for example, when the patch is subjected to tensile movements, otherwise the flat channel system 15 could tear without a tensile reserve.

In FIG. 9, a similar arrangement is shown, with the plaster having yet another self-adhesive layer 19 for attaching the systems to the skin and, optionally, additional dosage control of the active ingredient.

In FIG. 10 shows an arrangement with tape containers having the function of distribution chambers 14 for the active substance. This FIG. in this case, the plan view of the system according to the invention after the backing layer 10 has been removed. Clear break lines 17 can be clearly seen here, which can be used here to arbitrarily reduce or change the dispensing system. This embodiment is also very advantageous for pressure-applied patches.

In all the forms shown in FIG. further, bag-like films may be provided between the active agent-containing composition and the distribution matrix 12 to further limit the active agent reservoir so as to better delimit the active-substance-containing liquid or liquid active-substance.

Claims (10)

PATENT CLAIMS Transdermal therapeutic system for dispensing active substances on the skin, with the backsheet facing away from the skin, the active substance reservoir, the active substance dispensing control device, the active substance dispensing control system and the self-adhesive fixation device for adhering the therapeutic system to the skin, wherein the active substance reservoir is a multi-chamber system in which the distribution chambers (14) which are separated contain at least one active substance, wherein at least one pressure-sensitive adhesive layer (19) is provided between the backing layer (10) and the fixation device. Transdermal therapeutic system according to claim 1, characterized in that the distribution chambers (14) are at least partially interconnected by channels (15). Transdermal therapeutic system according to claim 1 or 2, characterized in that the distribution chambers (14) optionally have different devices for controlling the dosage of the active substance. Transdermal therapeutic system according to claim 1 or 2, characterized in that the distribution chambers (14) are arranged in at least one distribution matrix (12,12 ') for the active substance. Transdermal therapeutic system according to claim 1, characterized in that it has, on the skin side, an optionally interrupted self-adhesive skin-fixing layer (19). The transdermal therapeutic system of claim 1 1, characterized in that the active substance is liquid or soluble in a suitable, physiologically compatible solvent. Transdermal therapeutic system according to claim 1 or 2, characterized in that the multi-chamber system has the desired breakage between the individual active substance distribution chambers (14) and, optionally, in the backsheet (10) and the other layers. The transdermal therapeutic system of claim 2, characterized in that the channels (15) between the distribution chambers (14) have an internal diameter corresponding to the fluid flow rate of the active substance flowing only under pressure. The transdermal therapeutic system of claim 4 SK 277758 ku6 to 1, characterized in that the multi-chamber system is designed as a channel system (15). The transdermal therapeutic system of claim 1 or 2, characterized in that the distribution chambers (14) are arranged in different levels of plaster height or in different distribution matrices (12).